Systemic Treatment in Malignant Peripheral Nerve Sheath Tumors: Current Practice and Future Possibilities

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with a high risk of metastasis. Surgery is the mainstay treatment of localized MPNST, and the use of (neo)adjuvant systemic treatment in these cases is controversial. In pediatric cases, the use of chemotherapy is more common. Once metastasized, prognosis is poor, and systemic treatment is often the only treatment option despite limited response rates. MPNSTs as part of neurofibromatosis type 1 (NF1) are even less sensitive to chemotherapy. Apart from cytotoxic treatment, the tyrosine kinase inhibitor pazopanib is the only approved targeted drug for STS including MPNST. Noncytotoxic treatment regimens are still being investigated to target tumor-specific pathways, but to date, no trials have yet shown beneficial effects in MPNST. As the loss of the NF1 gene leads to Ras activation, targeting downstream pathways seems logical. But because of the biological heterogeneity among MPNSTs, a combination of therapies, including the targeting of upregulated receptor tyrosine kinases, angiogenesis, or nuclear targets, will likely yield the best results. The use of immunotherapy and oncolytic viruses seems promising as well but has also yet to show efficacy in a trial. Fortunately, many trials are still ongoing that will hopefully provide us with further evidence and possible treatment options in the near future. As the role of chemotherapy is still evolving in nonmetastatic MPNST, its use should ideally be discussed early on in a multidisciplinary team in a case-by-case setting with special attention to the anticipated merit in NF1-associated MPNST.